CCDC61/VFL3 Is a Paralog of SAS6 and Promotes Ciliary Functions.


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Authors
Ochi, Takashi 
Quarantotti, Valentina 
Lin, Huawen 
Rosa E Silva, Ivan 
Abstract

Centrioles are cylindrical assemblies whose peripheral microtubule array displays a 9-fold rotational symmetry that is established by the scaffolding protein SAS6. Centriole symmetry can be broken by centriole-associated structures, such as the striated fibers in Chlamydomonas that are important for ciliary function. The conserved protein CCDC61/VFL3 is involved in this process, but its exact role is unclear. Here, we show that CCDC61 is a paralog of SAS6. Crystal structures of CCDC61 demonstrate that it contains two homodimerization interfaces that are similar to those found in SAS6, but result in the formation of linear filaments rather than rings. Furthermore, we show that CCDC61 binds microtubules and that residues involved in CCDC61 microtubule binding are important for ciliary function in Chlamydomonas. Together, our findings suggest that CCDC61 and SAS6 functionally diverged from a common ancestor while retaining the ability to scaffold the assembly of basal body-associated structures or centrioles, respectively.

Description
Keywords
CCDC61, Chlamydomonas, SAS6, VFL3, XRCC4, basal body, centriole, centrosome, cilia, microtubule, structural biology, Algal Proteins, Cell Cycle Proteins, Cell Line, Chlamydomonas, Cilia, Crystallography, X-Ray, HEK293 Cells, Humans, Microtubule-Associated Proteins, Microtubules, Models, Molecular, Phylogeny, Protein Conformation, Protein Domains, Protein Multimerization
Journal Title
Structure
Conference Name
Journal ISSN
0969-2126
1878-4186
Volume Title
28
Publisher
Elsevier BV
Sponsorship
Cancer Research UK (18796)
Wellcome Trust (206388/Z/17/Z)
Engineering and Physical Sciences Research Council (EP/M017982/1)
Wellcome Trust (207510/Z/17/Z)
Wellcome Trust (101050/Z/13/Z)
Medical Research Council (MR/P000479/1)
Wellcome Trust (200814/Z/16/Z)